Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25753 | 77482;77483;77484 | chr2:178568875;178568874;178568873 | chr2:179433602;179433601;179433600 |
| N2AB | 24112 | 72559;72560;72561 | chr2:178568875;178568874;178568873 | chr2:179433602;179433601;179433600 |
| N2A | 23185 | 69778;69779;69780 | chr2:178568875;178568874;178568873 | chr2:179433602;179433601;179433600 |
| N2B | 16688 | 50287;50288;50289 | chr2:178568875;178568874;178568873 | chr2:179433602;179433601;179433600 |
| Novex-1 | 16813 | 50662;50663;50664 | chr2:178568875;178568874;178568873 | chr2:179433602;179433601;179433600 |
| Novex-2 | 16880 | 50863;50864;50865 | chr2:178568875;178568874;178568873 | chr2:179433602;179433601;179433600 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | None | None | None | N | 0.08 | 0.066 | 0.0954503805726 | gnomAD-4.0.0 | 3.60098E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.93752E-06 | 0 | 0 |
| S/Y | rs1286606791  |
-0.402 | 0.912 | N | 0.377 | 0.26 | 0.528009843598 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| S/Y | rs1286606791 |
-0.402 | 0.912 | N | 0.377 | 0.26 | 0.528009843598 | gnomAD-4.0.0 | 2.73806E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59846E-06 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0772 | likely_benign | 0.0757 | benign | -0.506 | Destabilizing | None | N | 0.08 | neutral | N | 0.394307158 | None | None | N |
| S/C | 0.1285 | likely_benign | 0.1349 | benign | -0.38 | Destabilizing | 0.928 | D | 0.339 | neutral | N | 0.514211919 | None | None | N |
| S/D | 0.2748 | likely_benign | 0.289 | benign | 0.016 | Stabilizing | 0.241 | N | 0.206 | neutral | None | None | None | None | N |
| S/E | 0.4197 | ambiguous | 0.425 | ambiguous | 0.084 | Stabilizing | 0.388 | N | 0.207 | neutral | None | None | None | None | N |
| S/F | 0.2105 | likely_benign | 0.2289 | benign | -0.796 | Destabilizing | 0.773 | D | 0.385 | neutral | N | 0.495626159 | None | None | N |
| S/G | 0.0719 | likely_benign | 0.0743 | benign | -0.763 | Destabilizing | 0.116 | N | 0.25 | neutral | None | None | None | None | N |
| S/H | 0.3264 | likely_benign | 0.3421 | ambiguous | -0.925 | Destabilizing | 0.69 | D | 0.349 | neutral | None | None | None | None | N |
| S/I | 0.1701 | likely_benign | 0.1771 | benign | 0.084 | Stabilizing | 0.69 | D | 0.383 | neutral | None | None | None | None | N |
| S/K | 0.6308 | likely_pathogenic | 0.6544 | pathogenic | -0.104 | Destabilizing | 0.241 | N | 0.205 | neutral | None | None | None | None | N |
| S/L | 0.1023 | likely_benign | 0.1116 | benign | 0.084 | Stabilizing | 0.241 | N | 0.315 | neutral | None | None | None | None | N |
| S/M | 0.1501 | likely_benign | 0.156 | benign | -0.139 | Destabilizing | 0.818 | D | 0.346 | neutral | None | None | None | None | N |
| S/N | 0.0855 | likely_benign | 0.0872 | benign | -0.38 | Destabilizing | 0.001 | N | 0.095 | neutral | None | None | None | None | N |
| S/P | 0.4319 | ambiguous | 0.4502 | ambiguous | -0.081 | Destabilizing | 0.773 | D | 0.391 | neutral | N | 0.493892575 | None | None | N |
| S/Q | 0.4354 | ambiguous | 0.4426 | ambiguous | -0.329 | Destabilizing | 0.69 | D | 0.373 | neutral | None | None | None | None | N |
| S/R | 0.6088 | likely_pathogenic | 0.6438 | pathogenic | -0.096 | Destabilizing | 0.388 | N | 0.361 | neutral | None | None | None | None | N |
| S/T | 0.0676 | likely_benign | 0.0694 | benign | -0.336 | Destabilizing | 0.001 | N | 0.089 | neutral | N | 0.384530095 | None | None | N |
| S/V | 0.1523 | likely_benign | 0.1538 | benign | -0.081 | Destabilizing | 0.241 | N | 0.308 | neutral | None | None | None | None | N |
| S/W | 0.4327 | ambiguous | 0.469 | ambiguous | -0.927 | Destabilizing | 0.981 | D | 0.429 | neutral | None | None | None | None | N |
| S/Y | 0.1968 | likely_benign | 0.2171 | benign | -0.52 | Destabilizing | 0.912 | D | 0.377 | neutral | N | 0.47902191 | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.